"A PROCESS FOR THE PREPARATION OF 14B-HYDROXY-1,14-CARBONATE-DEACETYLBACCATIN III"

Abstract

The present invention relates to a process for the preparation of 14ß-hydroxy-l,14-carbonate-deacetylbaccatin III, which comprise the following, steps: protection of the hydroxyls at the 7- and 10- positions of 10-deacetylbaccatin III, wherein R and R1 are trichloroacetyl, with trichloroacetyl chloride in methylene chloride in the presence of triethylamine and of catalytic amounts of N,N-dimethylaminopyridine; two-step oxidation to give the derivative oxidized to carbonyl at the 13-position and hydroxylated at the 14-position: in which the oxidation of the hydroxyl at the 13-position and the hydroxylation at the 14-position are effected with manganese dioxide or bismuth dioxide in a solvent selected from acetonitrile, acetone or ethyl acetate/methylene chloride mixtures; carbonation of the vicinal hydroxyls at the 1- and 14-position with phosgene in mehtylene chloride/toluene mixture in the presence of pyridine to give the 1, 14-carbonate derivative: reduction of the carbonyl at the 13-position with sodium borohydride in methanol: removal of the protective groups at the 7- and 10-position to give 14ß-hydroxy-l,14-carbonate-deacetylbaccatin III.

We claim:
1. A process for the preparation of 14ß-hydroxy-l ,14-carbonate-deacetylbaccatin III, which comprise the following, steps:
a. protection of the hydroxyls at the 7- and 10- positions of 10-
dcacetylbaccatin III:
(Figure Removed)
wherein R and R1 are trichloroacctyl, with trichloroacetyl chloride in methylene chloride in the presence of triethylamine and of catalytic amounts of N,N-dimethylaminopyridine;
b. two-step oxidation to give the derivative oxidized to carbonyl at the 13-
position and hydroxylated at the 14-position:
(Figure Removed)
in which the oxidation of the hydroxyl at the 13-position and the hydroxylation at the 14-position are effected with manganese dioxide or bismuth dioxide in a solvent selected from acetonitrile, acetone or ethyl acetate/methylene chloride mixtures;
c. carbonation of the vicinal hydroxyls at the 1- and 14-position with
phosgene in mehtylene chloride/toluene mixture in the presence of
pyridine to give the 1, 14-carbonate derivative:
(Figure Removed)
d. reduction of the carbonyl at the 13-position with sodium borohydride in
methanol:
(Figure Removed)
e. removal of the protective groups at the 7- and 10-position to give 14ß-
hydroxy-1,14-carbonate-deacetylbaccatin III.
2. The following reaction intermediate:
13-dehydro-14ß-hydroxy-7,10-bistrichloroacetyl-baccatin III 1,14-carbonate, as obtained in step b) as claimed in claim 1.
3. A process for the preparation of 14ß-hydroxy-1,14-carbonate-dcacetylbaccatin III substantially as herein described with reference to the foregoing description , examples, tables and the accompanying drawings.